Calcium homeostasis

Question 1

Roles of calcium (5)

Answer 1

Signalling - for exocytosis of vesicles, muscle contraction

Blood clotting - essential part of clotting cascade

Apoptosis

Skeletal strength

Membrane excitability - calcium decreases sodium permeability

Question 2

What effect does hypocalcaemia have on neuronal Na+ permeability

Answer 2

increases Na+ permeability leading to hyper excitation of neurons

Question 3

What effect does hypercalcaemia have on neuronal Na+ permeability

Answer 3

decreases neuronal Na+ permeability which will reduce excitability and depress neuromuscular activity

Question 4

Percentage distribution of calcium in the body (divided into 3 places)

Answer 4

Bones - 99%

Intracellular (mainly stored in mitochondria and sarcoplasmic reticulum) - 0.9%

Extracellular fluid - 0.1%

Question 5

0.1% calcium in the body is distributed in the ECF, how much of this is physiologically active

Answer 5

Only 0.05% as the other 0.05% is bound to carrier proteins like albumin or globulins so is not free in solution

Question 6

99% of calcium in the body is distributed in bone - how is it stored in bone

Answer 6

in the form of hydroxyapatite, in the extracellular matrix of bone

Question 7

Conc. of calcium in the plasma (i.e. ECF)

Conc. of physiologically active calcium in the plasma (i.e. free in solution)

Answer 7

2. 2-2.6mM (av. 2.4mM)

1. 2mM (as 50% Ca2+ in ECF is unbound, therefore free and ionised)

Question 8

What minerals does hydroxyapatite consist of (2)

Answer 8

Calcium + phosphate

Question 9

0.1% calcium that is distributed in the ECF (blood) is further sub-distributed in what 3 ways

Answer 9

40% bound to protein

50% free in solution

10% complexed with anions, e.g. bicarbonate, phosphate, to form calcium carbonate/phosphate etc

Question 10

The binding capacity of plasma proteins to Ca2+ is affected by what

Answer 10

pH

-binding capacity is increased under alkaline conditions

Question 11

How does hyperventilation affect the binding capacity of plasma proteins to Ca2+

Answer 11

binding capacity is increased under alkaline conditions so hyperventilating would cause plasma proteins to bind more Ca2+ as hyperventilating means you’re breathing out more CO2 so making blood more alkaline

May lead to hypocalcaemic tetany (involuntary contraction of muscle as neuronal permeability to Na+ is increased so progressive depolarisation)

Question 12

How does alkalosis increase the binding capacity of plasma proteins to calcium (acidosis therefore opposite)

Answer 12

in alkalosis, protons are deprotonated (i.e. loss of hydrogen ions bound to plasma protein which frees up binding spaces for Ca2+)

so the overall resulting negative charge on the protein allows Ca2+ to bind, thus reducing the amount of ionised calcium whilst total extracellular Ca2+ remains constant

whereas acidosis, there’s increased plasma hydrogen ions so they’d displace the Ca2+ bound to plasma proteins and increase the amount of free ionised Ca2+

Question 13

The 99% calcium store in bone functions to provide mechanical support but function is prioritised over this

Answer 13

Maintaining Ca2+ balance by releasing its calcium stores into the blood when needed TO MAINTAIN 1.2mM physiologically active plasma calcium

Question 14

What are osteoblasts + function

Answer 14

Bone building cells

-lay down collagen matrix which then calcifies into bone

Question 15

What do osteoblasts differentiate into

Answer 15

Osteocytes when established in bone

Question 16

Function of osteocytes

Answer 16

regulate the activity of osteoblasts and osteoclasts

- much less active than osteoblasts

Question 17

What are osteoclasts + function

Answer 17

Bone resorbing/destructing cells

• mobilise bone to allow release of its Ca2+ stores
• —-> does this by secreting H+ to dissolve calcium salts and provide proteolytic enzymes to digest the extracellular matrix and release Ca2+ into blood

Question 18

Explain the overall effect of PTH on plasma Ca2+ and phosphate concentrations

Answer 18

To increase concentration of free plasma Ca2+ (i.e. Ca2+ that is not bound to carrier protein)

Decreases plasma phosphate concentrations which in turn elevates free plasma Ca2+ conc. as it’s prevented from being deposited back into bone, as that process requires phosphate

Question 19

What is calcitriol + what organs is it produced by

Answer 19

Active form of vitamin D (vitamin D3)

Steroid hormone produced from vitamin D by liver AND kidneys (first step is in liver)

Question 20

Describe the 5 different mechanisms in which PTH increases free plasma Ca2+ conc.

Answer 20

Stimulates osteoclasts (BONE) to INCREASE RELEASE OF Ca2+ and phosphate into blood

Inhibits osteoblasts to reduce Ca2+ deposition in bone

Increases REABSORPTION OF Ca2+ from KIDNEY tubules, so decreasing its excretion in urine

Increasing RENAL EXCRETION OF PHOSPHATE, which elevates free plasma Ca2+ by preventing it from being deposited back into bone (a process that requires phosphate)

Stimulate the kidney to synthesise CALCITRIOL from vitamin D to promote calcium absorption at the gut and kidney

Question 21

What relationship does calcitriol have with PTH

Answer 21

It complements the action of PTH to increase plasma Ca2+ conc.

Question 22

In what 2 ways can be obtain calcitriol (active vitamin D3) (2)

Answer 22

From dietary vitamin D

UV light on skin –> activating endogenous (internal) precursors of vitamin D

Question 23

Primary action of calcitriol (activated form of vitamin D by kidney) + other actions (2)

Answer 23

Increase Ca2+ absorption form gut by active transport form intestinal lumen into blood

Facilitates renal absorption of Ca2+

Mobilises Ca2+ stores in bone by stimulating osteoclast activity

*Goal of calcitriol is to increase plasma Ca2+ conc. like PTH

Question 24

Increased levels of PTH stimulate the kidneys to release what

Answer 24

Calcitriol

Question 25

Calcitriol (active vitamin D3) formation is stimulated when there’s low plasma Ca2+, how else can it be stimulated in women

Answer 25

By prolactin hormone in lactating women

-stimulates kidney to synthesise calcitriol due to increased demand for Ca2+ for milk production

Question 26

Effect of PTH on renal formation of 1, 25 – dihydroxycholecalciferol (CALCITRIOL)

Answer 26

PTH stimulates release of calcitriol (1, 25 dihydroxycholecalciferol)

Question 27

Effect of 1, 25 - dihydroxycholecalciferol (CALCITRIOL) on calcium absorption from the gut

Answer 27

Increases Ca2+ absorption from gut

Question 28

Are circulating levels of calcitriol (1, 25 dihydroxycholecalciferol) low or high in:

• vitamin D deficient individuals
• pregnant/lactating women

+ why

Answer 28

Low - as calcitriol is derived from vitamin D so would be low if little vitamin D
–> due to less dietary Ca2+ absorbed than usual

High - lactating women produce prolactin hormone stimulates kidneys to release calcitriol due to an increased need for Ca2+ in milk production
–> due to more dietary Ca2+ absorbed than usual

Question 29

If deficient in vitamin D, then deficient in calcitriol so what effect does this have on PTH and plasma Ca2+ conc.

Answer 29

Calcitriol deficiency means decreased intestinal absorption of Ca2+ so decrease in plasma Ca2+ conc. therefore increasing PTH secretion which promotes phosphate deficiency –> aggravating Ca2+ loss from bone

PTH has to work alone to maintain plasma Ca2+ conc. and does so by continually removing Ca2+ from bone which sacrifices bone strength

Question 30

Vitamin D deficiency can lead to what conditions in children/adults

Answer 30

children - rickets

adults - osteomalacia

Question 31

Name a hormone that decreases plasma Ca2+ conc. (so unlike PTH and calcitriol)

Answer 31

Calcitonin

Question 32

What type of hormone is calcitonin + what is it produced by

Answer 32

Peptide hormone

Thyroid gland

Question 33

Main stimuli of calcitonin

Answer 33

Increased plasma Ca2+ conc.

Acts to decrease this

Question 34

Mechanisms of calcitonin in decreasing plasma Ca2+ conc. (2)

Answer 34

Bind to osteoclasts and inhibit bone resorption (release into blood)

Increase renal excretion to prevent further increase in plasma Ca2+

Question 35

Although calcitonin functions to decrease plasma Ca2+ conc. when it’s high, evidence suggests what about its importance in humans

Answer 35

Not that important because if calcitonin levels are very high or if no calcitonin is secreted at all, plasma Ca2+ levels are still normal

So excess calcitonin is OVERRIDDEN BY PTH

Question 36

In short, what effect does acidosis and alkalosis have on FREE IONISED plasma Ca2+

Answer 36

Acidosis increases free ionised plasma ca2+ - less Ca2+ bound to plasma protein as more H+ bound to them

Alkalosis decreases it - as more Ca2+ bound to plasma protein

Question 37

Parathyroid glands secrete what

Answer 37

Parathyroid hormone

Question 38

What 2 cell types is each parathyroid gland made up of

Answer 38

Chief cells

Oxyphil cells

Question 39

Function of chief cells of the parathyroid glands

Answer 39

produce and secrete PTH in response to low extracellular calcium

Question 40

How is vitamin D metabolised into a biologically active form (dietary and sunlight vitamin D is inactive)

Answer 40

First hydroxylated by vitamin D hydroxylase into 25-hydroxycholecaiferol (calcidiol), which is the major circulatory form of the vitamin

then

converted in kidney into 1,25-dihydroxycholecalciferol (CALCITRIOL) - biologically active